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Ophthalmic Signs in Practice of Medicine

Amod Gupta

Reema Bansal

Aman Sharma

Arun Kapil

Ophthalmic Signs in Practice of Medicine

Amod Gupta • Reema Bansal

Aman Sharma • Arun Kapil

Ophthalmic Signs in Practice of Medicine

Amod Gupta

Advanced Eye Centre, Chandigarh

Post Graduate Institute of Medical Education and Research

Chandigarh, India

Aman Sharma

Department of Internal Medicine

Post Graduate Institute of Medical Education and Research

Chandigarh, India

Reema Bansal

Advanced Eye Centre, Chandigarh

Post Graduate Institute of Medical Education and Research

Chandigarh, Chandigarh, India

Arun Kapil

Advanced Eye Centre, Chandigarh

Post Graduate Institute of Medical Education and Research

Chandigarh, India

ISBN 978-981-99-7922-6 ISBN 978-981-99-7923-3 (eBook) https://doi.org/10.1007/978-981-99-7923-3

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023

This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specifcally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microflms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifc statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affliations.

This Springer imprint is published by the registered company Springer Nature Singapore Pte Ltd. The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore

Paper in this product is recyclable.

Dedicated to my wife Gunita, daughter Sumedha, and son-inlaw Sachin for always standing by me; my students for keeping me au courant for more than 45 years of my academic career and above all, my patients, who reposed their complete trust in my ability to serve them and learn from them.

—Amod Gupta

Dedicated to my mentor, Prof Amod Gupta, who taught and inspired me at every step of my training in uveitis and vitreoretina, for his constant support and motivation; my family for being proud of me and for being my pillar of strength; my friends for their love and trust; and my patients for believing me and my abilities to treat them, and for also being a constant source of my learning.

—Reema Bansal

Dedicated to my father, Balbir Parkash Sharma, my guiding light; my mother, Sudesh Sharma, my pillar of strength; my sister, Kusum Sharma, who thinks her brother can do anything; my wife, Sushmita Sharma, who always stood by me and dealt with my absence without any complaints and my loving daughters, Ananya and Sharanya, who are my lifelines.

—Aman Sharma

To my Mentor, Prof. Amod Gupta for raising me to believe that anything is possible. I feel blessed and proud of working under his guidance for over 30 years. To Prof. Vishali Gupta, Retina Head, for her continuous motivation.

To my wife, Suman Kapil, for continuous support and encouragement in every step of my life. To my daughter, son-inlaw, son, daughter-in-law, family and friends, and grandsons.

Foreword

The quest to become an ophthalmologist has become increasingly popular and competitive. This may be because vision is our most precious sense. An ophthalmologist has the skill to preserve vision and, in some instances, to restore vision with just a few delicate motions in an operating theatre. The attraction lies in the fact that ophthalmology has a major role in some of the greatest recent medical advances, such as gene therapy and the application of technology to image anatomy and pathology. For many, ophthalmology affords the rewards of internal medicine and surgery. The cornea’s clarity allows the retina and brain to process light and the curious physician to look inward. And if that physician is knowledgeable and prepared, properly examining a tiny space, 2.5 cm from cornea to optic nerve, might reveal many secrets hidden elsewhere in the body.

In Ophthalmic Signs in the Practice of Medicine, four experts from the Postgraduate Institute of Medical Education and Research in Chandigarh, India, share their considerable wisdom and experience so that others may also skilfully interrogate the eye for clues to diagnosis and therapy. It is vital to understand that this is an interdisciplinary group led by Amod Gupta, a distinguished emeritus Professor of Ophthalmology. He is assisted by another talented ophthalmologist, Reema Bansal, a prolifc rheumatologist, Aman Sharma, and an expert in capturing images of the eye, Arun Kapil. Their insights provide a comprehensive resource which will be of value to the experienced practitioner who has examined the eye for decades, the internist who wishes to understand more fully the secrets of the eye, or the novice who is still in training and unsure if ophthalmology is the discipline most attractive to pursue.

We should be grateful to these authors for the considerable effort to assemble this volume. I am confdent that patients will be among the many benefciaries of their insights.

Legacy Devers Eye Institute

Portland, OR, USA, Corvus Pharmaceuticals Burlingame, CA, USA

February 28, 2023

James T. Rosenbaum

Foreword

Ophthalmology is one of the areas more internists fnd most diffcult to assess and interpret. This book Ophthalmic Signs in the Practice of Medicine is a much-needed book for all general physicians and internists.

The eye is an organ that offers a window into many disease processes. The absence of ophthalmic signs in many books on Medicine is serious lacunae that the authors are addressing with this book.

The book authored by Amod Gupta, Reema Bansal, Aman Sharma, and Arun Kapil is nicely structured with chapters on all signs. The extensive emphasis on retinal vasculature is excellent and offers the reader clear guidance on interpreting these signs.

The extensive use of high-quality illustrations makes this book stand out for me.

Ophthalmic signs are spotters; like skin, clinical examination skills are paramount. Ophthalmology is the last bastion where clinical examination skills still reign supreme as the rest of Medicine is taken over by emphasis on laboratory tests and imaging over clinical examination skills.

This book is of value to medical students, postgraduate trainees in general medicine, trainees in ophthalmology and general practitioners.

The authors are to be congratulated for bringing this book to help diagnose and assess ocular signs. In the new era of “precision medicine”, it is more important that clinicians (internists and ophthalmologists) understand each other’s language and work closely to improve the outcome of multisystem disease with ocular manifestations.

Paediatric Rheumatology, Bristol Royal Hospital for Children

Athimalaipet V. Ramanan, Bristol, UK February 27, 2023

Foreword

It gives me great pleasure to write the foreword to Ophthalmic Signs in the Practice of Medicine not only because one of the authors, Professor Amod Gupta, is a friend of many years but also because this book enables us to share the vast knowledge and expertise of an internationally renowned authority in the fields of uveitis and retinal diseases. He is joined by prolific contributors to the medical sciences, Prof. Reema Bansal, a professor of Ophthalmology; Prof. Aman Sharma, a Professor of Rheumatology and internal medicine and Arun Kapil, one of the most experienced clinical photographers.

Whereas most ophthalmic textbooks are organised according to anatomic or pathogenetic classifcations, this takes a different approach. Each chapter focuses on a specifc sign (e.g. cotton wool spots) and describes its signifcance, clinical features and pathogenesis. A differential diagnosis of the sign itself (e.g. cotton wool spots versus medullated nerve fbres) is followed by the list of ocular or systemic conditions associated with the presence of the sign in question. Most of these conditions are listed and the subject of a comprehensive overview of their pathogenesis, clinical features and, when relevant, therapeutic possibilities. Therefore, more than being a guide to the differential diagnosis of retinal conditions based on clinical signs, this book also doubles as an excellent and up-to-date treatise of retinal diseases. For instance, reading and absorbing the chapters on cotton wool spots, hard exudates, microaneurysms and new vessels will provide the reader with solid knowledge of the pathogenesis, clinical features and treatment of diabetic retinopathy.

Each chapter is extensively referenced and profusely illustrated. The many recent papers from 2020, 2021 and 2022 testify to the authors’ successful effort to include the most recent knowledge. The high quality of the illustrations (colour photographs, wide feld fundus imaging, fuorescein angiography, OCT and OCT-A) substantially adds to the book’s quality.

Without hesitation, I would recommend this textbook to train residents: starting from observing a clinical sign in their patient, this textbook will take them on a fascinating journey to explore the rich world of retinal pathology.

The established practitioner who wants to update his or her knowledge on retinal pathology will not fnd a better source. As an additional bonus, he or she will beneft from the many clinical pearls the authors share with the reader, wisdom collected during distinguished careers as clinician-scientists.

University of Ghent Philippe Kestelyn, Ghent, Belgium

March 26, 2023

Preface

The human eyes are often called the windows to the body in health and disease. Eyes provide an extraordinary insight into our overall health. The eyes are the only part of the body where a physician, using non-invasive tools, can directly visualize pathology as it is evolving, often decades before manifesting as a grave systemic disorder.

Within these small, though intricate organs lies a world of valuable information that can provide vital insights into a person’s well-being. Ophthalmic signs, the tell-tale indicators in the eyes, are remarkable signatures of underlying systemic diseases. From the subtlest of changes to the most pronounced abnormalities, these signs can offer a glimpse into the intricate workings of the human body.

Artifcial compartmentalization and increasing sub-specialization in every feld of medicine, beginning in the latter half of the twentieth century, rapidly created silos of excellence that can deal successfully with the most complicated diseases, often at the cost of missing clues to the earliest onset of the disease. Unlike when the ophthalmic examination was an integral part of the patient workup, heavy demand on the trainees’ time in different subspecialties has dramatically reduced the captive time for exposure to ophthalmology and the ophthalmic signs.

Ophthalmology is a highly visual science wherein such signs can be easily learnt, objectively documented, and used in clinical practice to improve quality of care, early diagnosis, and appropriate referrals. In medicine, recognizing and interpreting ophthalmic signs has proven to be an invaluable tool.

The eyes are integral to the body’s systems and share structural, physiological, immunological, biochemical, neurological, and biological homology and pathways. The eyes often reveal the consequences of systemic disorders, chronic diseases, and genetic disorders. Not only do these signs aid in diagnosing ocular disorders, but they can also serve as early warning signals for a myriad of systemic diseases.

This book, profusely illustrated, delves into the fascinating realm of ophthalmic signs, exploring their diverse manifestations and signifcance in medicine. Through an in-depth exploration of various eye conditions, their associated signs and pathogenetic mechanisms, we aim to empower clinicians, family physicians, medical students, residents, and fellows in training with the knowledge and skills necessary to detect, evaluate, and interpret these invaluable clues.

Drawing upon the latest research and clinical experiences, this book seeks to enhance the understanding of ophthalmic signs as a crucial component of the diagnostic process. By highlighting the interplay between ocular health and systemic well-being, we hope to foster a holistic approach to patient care and encourage collaboration between ophthalmologists, general practitioners, internists, endocrinologists, neurologists, and specialists from various other medical disciplines.

Embark on this enlightening journey through the captivating realm of ophthalmic signs and witness how the eyes are extraordinary indicators of our overall health.

Chandigarh, India Amod Gupta Chandigarh, India Reema Bansal Chandigarh, India Aman Sharma Chandigarh, India Arun Kapil

Acknowledgements

We want to acknowledge several eminent ophthalmologists’ and researchers’ generosity in sharing their precious images with us, without which this book would have remained incomplete.

Dr Manphool Singhal, Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India, for fgures 1.13 and 18.7

Dr Alok Sen Sadguru Netra Chikitsalya, Chitrakoot, MP, India, for fgures 3.12, 3.18, 10.9B

Dr Simar Rajan Singh, Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India, for fgures 6.18 to 6.21

Prof Anjali Agarwal, Head, Department of Anatomy, Postgraduate Institute of Medical Education and Research, Chandigarh, for fgures 8.1, 15.1, 16.2, 20.1

Dr Anuradha V K, Head of Uveitis Services, Aravind Eye Hospital, Coimbatore, India, for Fig. 10.8A

Prof Ramandeep Singh, Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India, for Fig. 10.8B

Dr Padmamalini Mahendradas, Uveitis and Ocular Oncology, Narayana Nethralaya, Bangalore, India, for fgures 10.22 to 10.24

Dr Anita Agarwal, West Coast Retina Medical Group, San Francisco, CA 94109, for fgures 13.1, 13.7, 13.8, 13.10 to 13.15.

Dr Chirag Ahuja, Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India, for the interpretation of Fig. 1d.

Prof Daisy Sahni (Ex-Professor) Department of Anatomy, Postgraduate Institute of Medical Education and Research, Chandigarh, India, for Fig. 15.1

Dr SS Pandav, Professor and Head, Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India, for fgures 15.3, 15.16

Dr Rithambra Nada, Prof of Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India, for fgures 15.20 and 18.8B

Dr Chintan Malhotra, Professor, Cornea, Lens and Refractive Surgery Services, Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India, for fgures 17.3 to 17.13

Dr Anandita Sinha, Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India, for fgures. 17.14B and 17.17 (d, e)

Prof Pradeep Bambery, Ex-Professor of Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India, for Fig. 18.16

Dr Amit Gupta, Professor, Cornea, Lens and Refractive Surgery Services, Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India, for fgures 17.14 b–d, 18.6

Dr Kanwar Mohan, Dr Kanwar Mohan’s Squint Centre, Chandigarh, India, for fgures 19.5, 19.7, 19.15, 19.16, 19.18, 19.19, 19.20, 20.1b

Dr Manpreet Singh, Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India, for fgures 19.8c, 19.11e, 20.2, 20.6, 20.7

Dr Ali G. Hamedani, Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, United States, for fgures 19.10 and 19.12

Dr Anja K E Horn, Professor, Ludwig-Maximilian University Munich, Germany, for Fig. 19.21

Prof. Usha Singh, Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India, for fgures 20.4, 20.5, 20.8, 20.13, 20.17, 20.18, 20.19

Dr Pankaj Gupta, Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India, for Fig. 20.9

Dr Shweta Chaurasia, Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India, for fgures 20.10 to 20.12, 20.14, 20.15

Dr Kasturi Bhattacharjee, Sri Sankaradeva Nethralaya, Guwahati, India, for fgures 20.16, 20.20

Kritika Thakur for graphics—fgures 15.2; 16.3 to 16.6; 16.8 to 16.10; 19.1 to 19.4; 19.6; 19.8 a, b; 19.9; 19.11a–d; 19.13; 19.14; 19.22 to 19.26

We want to thank several publishers who allowed us to reuse our images published over several years in the past.

Publishers of Frontiers of Medicine for reusing Fig. 3.11 from our publication Bansal et al. (2021) Frontiers of Medicine 8:681942. doi: 10.3389/ fmed.2021.681942.

Publishers of Neurology for allowing us to reuse Fig. 5.15 from our publication Takkar et al. Neurology 2013,81:e40

Springer Singapore for allowing us to reuse Fig. 6.5 and Fig. 16.1 from our publication Gupta A (2022). Bench-to-Bedside Research in Ophthalmology. In: Sobti, R., Ganju, A.K. (eds) Biomedical Translational Research. Springer, Singapore. https://doi.org/10.1007/978-981-16-8845-4_5

Elsevier for allowing us to reuse Fig. 6.17 published by Chiang et al. (2021) in Ophthalmology. 2021 Oct;128(10):e51–e68. doi: 10.1016/j. ophtha.2021.05.031

Publisher for allowing us to reuse fgures 10.10C and 10.11B from our publication, Bansal et al. (2012) Expert Review of Ophthalmology, 7(4), 341–349. doi:10.1586/eop.12.42

Springer Berlin for Fig. 10.11C from our publication Gupta A (2016) in Zierhut et al. (eds) Intraocular Infammation. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-75387-2_105

Figure 12.7C from Singh et al. (2012) Medicine (Baltimore). 2012 Jul;91(4):179–194. doi: 10.1097/MD.0b013e3182574a0b. PMID: 22732948

Figure 14.12, Gupta A and Gupta V (2009) Paediatric uveitis in Gupta A et al. (eds) Uveitis: Text and Imaging 1st Edn. Jaypee Brothers Medical Publishers (P) Ltd., New Delhi. P 518

Fig. 15.15 from Gupta et al. (2012) BMJ Case Rep. 2012 Aug 21;2012:bcr2012006718. doi: 10.1136/bcr-2012-006718. PMID: 22914240

Figure 16.7 with permission from NeurOptics, inc. (Irvine, CA92612, USA)

Figure 17. 14a, 17.16a, 17.19, 17.20, 18.8, 18.15b, c, d from Bambery et al. (2009) Systemic examination and imaging in Gupta et al. (eds) Uveitis: Text and Imaging 1st Edn. Jaypee Brothers Medical Publishers (P) Ltd., New Delhi

Figure 17.18 from Gupta et al. (2009) Gupta et al. (eds). Uveitis: Text and Imaging 1st Edn. Jaypee Brothers Medical Publishers (P) Ltd., New Delhi

Figure 17.24 EyeNet Magazine, Agarwal AK et al., Pigmented Keratic Precipitates in Herpes Simplex Virus Anterior Uveitis November 2018

Figure 17.27 EyeNet Magazine,  Gupta AK, et al. September 2014

Figure 18.1, 18.13 from Sharma et al. In: Sharma A (ed).Textbook of Systemic Vasculitis, 1st Edn. Jaypee Brothers Medical Publishers (P) Ltd., New Delhi

We also thank publishers for allowing us to adapt/reuse material from their publications to create boxes for various chapters in our book.

Publishers to allow us to reuse/adapt from various publications for

Boxes 10.1 from Holland, 1994

Box 10.2. from Standardization of Uveitis Nomenclature (SUN) Working Group. Classifcation Criteria for Acute Retinal Necrosis Syndrome 2021

Box 10.3 from Standardization of Uveitis Nomenclature (SUN) Working Group. Classifcation Criteria for Cytomegalovirus Retinitis, 2021

Box 10.4 and 10.5 from Gupta et al. (2015) Classifcation of intraocular tuberculosis. Ocul Immunol Infamm. 2015 Feb;23(1):7–13. doi: 10.3109/09273948.2014.967358

Box 10.6 from Fig. 2 by Aringer et al. (2019)

Box 10.7 from Korsten et al. (2018)

Box 10.8 from Standardization of Uveitis Nomenclature (SUN) Working Group

Box 10.9 Classifcation Criteria for Sarcoidosis-Associated Uveitis, 2021 from Standardization of Uveitis Nomenclature (SUN) Working Group. Classifcation Criteria for Behçet Disease Uveitis, 2021

Box 10.9 from Criteria for diagnosis of Behçet’s disease. International Study Group for Behçet’s Disease, 1990.

Box 10.10 from O'Keefe and Rao from Surv Ophthalmol. 2017 JanFeb;62(1):1–25. doi: 10.1016/j.survophthal.2016.05.002. Epub 2016 May 27. PMID: 27241814

Box 14.1 from Lonser et al. (2003)

Box 14.2 from VHL Alliance, Boston, MA, 02284-4682 and 14.3 from Ophthalmology. 2006 Dec;113(12):2276–80. doi: 10.1016/j. ophtha.2006.06.018 Acknowledgements

Box 15.1 from Petzold et al. Lancet Neurol. 2022 Dec;21(12):1120–1134. doi: 10.1016/S1474-4422(22)00200-9

Box 15.2 Reproduced under the Creative Commons Attribution license (CC BY) from Szekeres and Othman Front Med (Lausanne). 2022 Dec 13;9:1066503. doi: 10.3389/fmed.2022.1066503. PMID: 36582285

Box 19.1 from Jaretzki et al. 2000. Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientifc Advisory Board of the Myasthenia Gravis Foundation of America. Ann Thorac Surg. 2000 Jul;70(1):327–34. doi: 10.1016/s0003-4975(00)01595-2. PMID: 10921745

Reviewers: We want to thank Dr Anita Agarwal, West Coast Retina Medical Group, San Francisco, CA, for the review of Chapters 7, 12, and 13 and Dr Aastha Takkar for the review of Chapters 15 and 16. We highly appreciate their valuable comments to improve the quality of our book.

Finally, we like to express our gratitude to Prof Jim Rosenbaum MD, Chair, Emeritus Legacy Devers Eye Institute, Portland, OR, USA, Prof Athimalaipet V Ramanan, FRCP, Professor of Paediatric Rheumatology, Bristol Royal Hospital for Children, Bristol, UK, and Prof Philippe Kestelyn, Emeritus Professor University of Ghent, Belgium, for fnding time from their extremely busy schedule to review our manuscript and write forewords for this book.

We like to thank Ms Sinchu Mohan, Ms Jagjit Kaur Saini, and Mr Naren Agarwal of Springer Team India for giving a fnal shape to our book

Amod Gupta MBBS; MS, Emeritus Professor, Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Reema Bansal MBBS, MS, PhD. Professor of Ophthalmology, Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Aman Sharma MD, FRCP (London). Professor of Medicine, Clinical Immunology and Rheumatology, Program Director, Centre of Excellence in HIV/AIDS,

Postgraduate Institute of Medical Education and Research, Chandigarh, India

Arun Kapil Senior ophthalmic technician, Chief, Digital Retina Imaging Laboratory, Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India Chandigarh

2.3.7 Other Systemic Associations 28

2.4 Ocular Associations of RAM 28

2.4.1 Congenital Retinal Arteriolar Anomalies

2.4.2 Idiopathic Retinal Vasculitis, Aneurysms, and Neuroretinitis (IRVAN) and RAM

2.4.3 Retinal Vein Occlusion

2.4.4 Toxoplasma

2.5 Clinical Presentations of RAM

2.5.1 Fusiform RAM

2.5.2 Saccular RAM 29

2.5.3 Retinal Capillary Macroaneurysms

2.6 Imaging of RAM

2.7 Treatment of RAM 33

2.8 Pathology of RAM

2.9 RAM Versus Intracerebral Arterial Microaneurysms 36 References

3.1 Introduction

3.2 Cotton Wool Spots Versus Medullated Nerve Fibres

3.3 Causes of Cotton Wool Spots

3.3.1

3.3.4 CWS in Systemic Lupus Erythematosus (SLE).

3.4 Imaging of the CWS

3.5 Paracentral Acute Middle Maculopathy (PAMM)

4.2 Causes of Retinal Hard Exudates

4.3 Differential Diagnosis of Retinal Hard Exudates

Hard Exudates Versus Soft Exudates

4.3.2 Hard Exudates Versus Drusen

4.4 Classifcation of Retinal Hard Exudates [2]

4.5 Signifcance of Retinal Hard Exudates

4.6 Formation of Retinal Hard Exudates

4.7 Hyperrefective Foci as Forme Fruste of Retinal Hard Exudates

4.8 Histopathology of Hard Exudates

4.9 Hard Exudates: A Surrogate for Atherosclerosis

4.10 Serum Lipids and Diabetic Retinopathy

4.10.1 Hyperlipidaemia and Diabetic Retinopathy

4.10.2 Role of Statins in Hard Exudates

4.11 Complications of Retinal Hard Exudates

4.12 Treatment of Retinal Hard Exudates Associated with Macular Oedema

Retinal Hard Exudates in Branch Retinal Vein Occlusion

4.13.2 Retinal Hard Exudates in Adult Coats’ Disease

4.13.3 Retinal Hard Exudates in Idiopathic Retinal Vasculitis, Aneurysms and Neuroretinitis (IRVAN) .

4.13.4 Retinal Hard Exudates in Von Hippel–Lindau Disease

Vitreous Haemorrhage

5.2.5 Dot and Blot Haemorrhages.

5.2.6 Petaloid Retinal Haemorrhages (Henle Haemorrhages)

5.5.1

5.5.5 Retinal Haemorrhages in Increased Intracranial Pressure 95

5.5.6 Valsalva Retinopathy . . . . . .

95 References 97

6 New Vessels on the Optic Disc and Elsewhere in the Retina . . . . 101

6.1 Introduction 101

6.1.1 Blood Supply of the Retina

6.1.2 Development of Normal Retinal Vessels .

102

102

6.2 Pathophysiology of Diabetic Retinopathy 102

6.2.1 Muller Cells .

102

6.2.2 Pericytes-Endothelial Cell Interaction 103

6.2.3 Thickening of Basement Membrane in Diabetes Mellitus

6.2.4 Consequences of the Basement Membrane Thickening

6.2.5 Formation of Acellular Retinal Capillaries .

6.2.6 Retinal Capillary Non-Perfusion and Severity of Diabetic Retinopathy .

6.2.7 Development of Retinal New Vessels . . . .

104

104

104

106

108

6.2.8 Intraretinal Microvascular Abnormalities (IRMA) 109

6.2.9 Retinal Veins Dilatation, Beading, and Risk of Progression 110

6.2.10 New Vessels on the Retina Elsewhere (NVE) and the Optic Disc (NVD) .

112

6.2.11 Automated Detection of New Vessels in Diabetic Retinopathy 116

6.2.12 Chronic Kidney Disease and Diabetic Retinopathy .

116

6.3 Other Causes of New Vessels on the Retina 117

6.3.1 Retinopathy of Prematurity (ROP) .

6.3.2 Familial Exudative Vitreoretinopathy (FEVR)

117

124

6.3.3 Sickle Cell Retinopathy 126 References

128 7 Subretinal/Submacular Haemorrhage 139

7.1 Introduction

7.2 Age-Related Macular Degeneration 140

7.3 Risk Factors for AMD 141

7.4 Pathogenesis of AMD

7.5 Clinical Signs of Age-Related Macular Degeneration 142

7.6 Current Nomenclature for AMD Lesions [1]

7.7 Imaging Studies in Macular New Vessels (MNV)

144

145

7.8 Polypoidal Choroidal Vasculopathy 147

7.9 Pathogenesis and Risk Factors for Polypoidal Choroidal Vasculopathy

7.10 Treatment of Polypoidal Choroidal Vasculopathy 151

7.11 Treatment of Massive Submacular Haemorrhage

152

7.12 Other Causes of Submacular Haemorrhage 155 References 156

8 Retinal Arteriolar Changes in Hypertension and Arteriolosclerosis

8.1 Structural Considerations of the Blood Vessels . .

8.1.1 Anatomical Considerations of the Central Retinal Artery and the Blood Supply of the Retina

8.1.2 Diameter of the Retinal Arterioles and Their Fractal Dimensions

8.2 Causes of Hypertension

8.3 Measuring Blood Pressure

8.5 Fundus Signs of Arteriolosclerosis and Hypertension

Focal and Diffuse Narrowing of the Retinal Arterioles

8.5.6

10.6.1 Toxoplasmic Retinochoroiditis 209

10.6.2 Infectious Herpes Simplex and Varicella Zoster Virus Retinitis

10.6.3 CMV Retinitis 215

10.6.4 Emerging Viral Infections and Retinitis .

219

10.6.5 Bacterial Infectious Uveitis-Spirochetal Infections 220

10.6.6 Other Bacterial Uveitis: Mycobacterium tuberculosis

10.7 Non-infectious Choroiditis and Retinitis 233

10.7.1 Systemic Immune-Mediated Disorders

233

10.7.2 Organ-Specifc (Ocular) Immune-Mediated Panuveitis with Multisystem Involvement 243

10.7.3 Organ-Specifc (Ocular) Immune-Mediated Disorders 251

10.8 Multiple Evanescent White Dot Syndrome (MEWDS) . .

10.9 Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE)

10.10 Punctate Inner Choroidopathy and Idiopathic Multifocal Choroidopathy (PIC and IMFC)

10.11 Acute Zonal Occult Outer Retinopathy (AZOOR) 256

10.12 Birdshot Chorioretinopathy (BCR)

10.13 Acute Macular Neuroretinitis (AMN)

Homeostasis in the Retinal Microenvironment

11.3 Examination of Retina and Documentation of Macular Oedema

11.3.1 Clinical Examination of the Macula

11.3.2 Documentation of Macular Oedema-Fundus Photography

11.3.3 Fundus Fluorescein Angiography

11.3.4 Optical Coherence Tomography 274

11.3.5 Measuring the Central Subfeld Thickness (CST) with OCT 275

11.4 Causes of Macular Oedema 276

11.4.1 Diabetic Macular Oedema

11.4.2 Macular Oedema in Retinal Vein Occlusions 289

11.5 Macular Oedema in Uveitis

11.5.1 Diagnosis of Macular Oedema in Uveitis

294

295

11.5.2 OCT Biomarkers in Uveitis Macular Oedema 296

11.5.3 Treatment of Uveitis Macular Oedema

11.5.4 Sustained-Release Corticosteroid Implants

11.5.5 Suprachoroidal Injection of Triamcinolone Acetonide Suspension

11.5.6 Alternative Strategies to Treat UME 298

Objective Measurement of Pseudophakic Cystoid Macular Oedema (PCME)

Incidence and Risk Factor for Post-surgery Macular

13 Macular Degeneration, Geographic Atrophy, and Inherited Retinal Disorders 351

13.1 Introduction . .

13.2 Anatomical Considerations 351

13.3 Complement Pathway-Basics .

13.4 Age-Related Changes in the Retina

13.5 Age-Related Macular Degeneration (AMD) 354

13.5.1 Epidemiology

13.5.2 Role of Complement Pathways in AMD

354

354

13.5.3 Risk Factors for AMD and Its Pathogenesis 354

13.5.4 Epigenetic Factors in Dry AMD

355

13.5.5 Clinical Diagnosis of AMD 355

13.5.6 Classifcation of AMD 356

13.6 Inherited Retinal Disorders

361

13.6.1 Introduction 361

13.6.2 Ancillary Lab Testing in Inherited Retinal Disorders

13.6.3 Non-syndromic Retinitis Pigmentosa: Clinical Signs

13.6.4 Leber Congenital Amaurosis

13.6.5 RPE 65-Associated LCA

13.6.6 CEP290-Associated Retinal Dystrophy

363

13.6.7 Primary Ciliopathies and RP 372

13.6.8 Systemic Diseases Associated with Inherited Retinal Degeneration

13.7 Inherited Macular Dystrophies

13.7.1 Stargardt’s Disease and Fundus Flavimaculatus (ABCA4 Disorders)

13.7.2 Bestrophinopathies

13.8 Mitochondrial Retinal Dystrophies

13.9 Treatment of Inherited Retinal Disorders

13.9.1 Gene Supplement Therapy

13.9.2 Antisense Oligonucleotide Treatment

13.9.3 Optogenetics

14 Vascular Malformations, Childhood Cancer Predisposition Syndromes and Their Systemic Associations 397

14.1 Introduction

14.2 Retinal Capillary Hemangioblastoma 398

14.2.1 Retinal Capillary Hemangioblastoma—Historical Aspects

14.2.2 Retinal Capillary Hemangioblastoma—Genetic Aspects

14.2.3 Retinal Capillary Hemangioblastoma—Systemic Associations 398

14.2.4 Retinal Capillary Hemangioblastoma (Angiomas) . 400

14.2.5 Treatment of von Hippel-Lindau’s Disease 403

14.2.6 Active Surveillance in VHL 403

Sturge-Weber Syndrome—Diffuse Choroidal Hemangioma

Circumscribed Choroidal Hemangiomas Are Not Associated with SWS

Sturge-Weber Syndrome—Neurological Associations

14.4 Arteriovenous Malformation of the Retina (AVM)— Wyburn-Mason Syndrome

15.3.8 OCT Angiography 431

15.3.9 Artifcial Intelligence for Automatic Diagnosis of Glaucomatous Optic Neuropathy . . . . 431

15.3.10 Myopia and Glaucomatous Optic Neuropathy 431

15.4 Choosing a Tool for Fundus Examination in Neuro-Ophthalmological Disorders

15.4.1 Optic Nerve Head Edema and Papilledema-Clinical Evaluation

15.4.2 Ocular Causes of ONH Swelling

432

435

436

15.4.3 Signs of Papilledema 436

15.4.4 Role of OCT in Papilledema

440

15.4.5 Psudopapilledema Due to Optic Disc Drusen 441

15.4.6 Papilledema in Idiopathic Intracranial Hypertension

442

15.5 Optic Neuritis—Infammation of the Optic Nerve 444

15.5.1 Epidemiology of Optic Neuritis

15.5.2 Evaluation of Optic Neuritis in the Clinic . . .

445

446

15.5.3 Diagnosis of Optic Neuritis 449

15.5.4 Multiple Sclerosis-Associated Optic Neuritis (MS-ON)

15.5.5 Pathogenic Antibody-Associated Optic Neuritis Syndromes

449

450

15.6 Optic Disc Pallor (Atrophy) 451

15.6.1 Inherited Optic Neuropathies 453

15.6.2 Chiasmal Compression Syndrome .

456

15.6.3 Ischaemic Optic Neuropathies (ION) 460

15.6.4 Posterior Ischaemic Optic Neuropathy (PION) . . . . 462

15.6.5 Arteritic Anterior Ischaemic Optic Neuropathy . . . . 463 References 465

Part II Extraocular Signs

16 Pupillary Signs

16.1 Anatomical Considerations

16.1.1 The Sphincter Pupillae 475

16.1.2 The Dilator Pupillae

16.1.3 The Ciliary Ganglion 475

16.1.4 Pupil Size 476

16.2 Pathway for the Pupil Light Refex

476

16.2.1 Sympathetic Pathway 478

16.3 Testing for Pupillary Refexes

16.3.1 Swinging Flashlight Test

480

481

16.3.2 Phases of Pupil Light Refex 481

16.3.3 Causes of RAPD .

481

16.4 Pupillary Changes in Lesions of Parasympathetic Pathways 481

16.5 Argyll Robertson Pupil

482

16.5.1 Automated Pupillometry 483

16.5.2 Neurological Pupil Index 484

18 Episcleritis, Scleritis, and Peripheral Corneal Ulceration 543

18.1 Sclera and Episclera-Anatomical Considerations 543

18.2 Episcleritis and Scleritis . . . . . . . . . . .

543

18.2.1 Epidemiology of Episcleritis and Scleritis 544

18.2.2 Etiology of Non-infectious Scleritis .

18.2.3 Etiology of Infectious Scleritis . . . . . . .

544

545

18.2.4 Clinical Characteristics of Episcleritis 546

18.2.5 Clinical Characteristics of Scleritis .

18.2.6 Surgically Induced Necrotizing Scleritis .

548

554

18.2.7 Complications of Episcleritis and Scleritis 554

18.2.8 Anterior Segment Optical Coherence Tomography to Differentiate Episcleritis from Scleritis 555

18.2.9 Differentiating Infectious from Autoimmune Scleritis 555

18.2.10 Pathogenesis of Scleritis

18.2.11 Pathology of Scleritis

556

556

18.2.12 Treatment of Episcleritis and Scleritis 556

18.3 Cornea-Anatomical Considerations . . . . . . . .

558

18.3.1 Epidemiology and Etiology of Peripheral Ulcerative Keratitis 558

18.3.2 Systemic Associations of Peripheral Ulcerative Keratitis 558

18.3.3 Peripheral Stromal Keratitis and Peripheral Ulcerative Keratitis

559

18.3.4 Para Central Corneal Melt-Pathogenesis 561

18.3.5 Mooren’s Ulcer

18.3.6 Pathology of PUK

18.3.7 Systemic Implications for PUK in Systemic Collagen Vascular Diseases

561

562

562

18.3.8 Pathogenetic Mechanism for Peripheral Ulcerative Keratitis 562

18.3.9 Treatment of PUK

563

18.3.10 Adjunctive Local Treatment to Restore the Integrity of the Globe 565 References

19 Lid Signs, Paralytic Squint, and Ocular Movement

Disorders

565

573

19.1 Lids: Anatomical Considerations 573

19.2 Anthropometry of Lids

19.3 Lid Signs

574

575

19.3.1 Ptosis 575

19.3.2 Lid Retraction of the Upper Eyelid

19.3.3 Lid Lag

580

581

19.3.4 Spontaneous Blinking 584

19.3.5 Blepharospasm

586

19.4 Extraocular Muscles- Anatomical Considerations

Oculomotor Nerve Paresis .

19.5.2 Recurrent Painful Ophthalmoplegic Neuropathy (Previously Labelled) Ophthalmoplegic Migraine)

Generalized Myasthenia Gravis

Ocular Myasthenia Gravis

Parks-Bielschowsky 3-Step Test-Diagnosing Paresis of a Cyclovertical Muscle

Diplopia

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problem stared him in the face in the light like an unsolved question, or the game that one goes to bed leaving unfinished; but with him and with her it would be the most important move in the game of their young and at present, divided lives—the lives and loves of two who were bound up in each other, all the more that they had no one to care for in this world save each other.

Meanwhile one anxious hour followed another, and there came no sound of troops on the sward—no clatter of accoutrements to announce that the pursuing Horse were returning his way.

The Second Division and Wood's Flying Column had marched to a mountain called the Entonjaneni, and there formed a camp about twenty miles distant from Ulundi as the crow flies. Vast quantities of thorn-bushes grew on the left of it, and before it spread an open plain; and to this camp came nearly the last envoys of Cetewayo, bearing two elephants' tusks as a sign of amity, promising a herd of cattle, and so forth. The tusks were declined, and the original conditions insisted on. However, Lord Chelmsford agreed to delay his final advance till the evening of the 29th of June.

Buller's Horse and the other mounted men were returning slowly from their long pursuit, when they drew near the kraals so recently destroyed, and saw that one hut was burning still, and casting a lurid light against the evening sky. All thought this strange, as before the repulse of the Zulus in the valley the fire in every kraal was completely over, as there seemed nothing more left to burn.

Suddenly Tom Tyrrell cried out, in a voice of the keenest excitement:

'The hut in which we left our officer is in flames—the poor fellow will be burned to death!'

'Who?' exclaimed Villiers.

'Our poor officer—Lieutenant MacIan.'

'God! you don't say so!'

'See for yourself, sir.'

'It is too evidently as you say. Forward at a gallop!'

The flames were sinking fast when they reached the hut, now reduced to a smouldering heap of ashes, and the horrible odour of burned human flesh overpowered the perfume of the wild flowers, amid which the great bees were yet humming; and poking amid the hot débris with their lances, the men of the 17th found the charred remains of what had been evidently a human body; and though inured to war, to bloodshed, and daily human suffering, the soldiers looked blankly and inquiringly in each other's faces, pausing for orders, and wondering what was to be done now.

In the hut the luckless Florian had lain for a time on its clay-beaten floor listening for every sound. He had a natural fear of Zulus coming upon him suddenly and assegaiing him in cold blood—if indeed the blood of these fierce savages was ever cold till death seized them.

The idea was intolerable; and he writhed on the hard floor and hearkened intently with his ear placed close thereto.

Shots in the far distance announced that fighting was going on somewhere—that Redvers Buller, the unwearied, was 'at it again'—but told him nothing more. What if the advanced troops were defeated—had to fall back towards the Entonjaneni Mountain by some other route, and had to abandon him to his fate?

In war, of what value is one human life, save to the proprietor thereof?

Anon, amid these exciting and oppressive thoughts, he became conscious of a singular and awful odour pervading the place. He had knowledge enough of it by ample past experience to know that it came from the body of a dead Zulu. He peered about, and in a corner hitherto unnoticed, near a pile of fresh bull-hides, intended doubtless for conversion into long shields, partly covered by one, lay the corpse of a Zulu warrior, whose shaven head, with the military ring or fillet, and bare feet, with anklets of burnished copper, were visible.

Pah!

Such a companion as this proved too much for his nerves, and at all risks —the risk of being seen by scouting Zulus—he crawled out of the hut into the pure and grateful air of heaven, and contrived to reach a clump of dwarf mimosa-trees at a little distance on the slope of an eminence, and therein he lay to await the return of his comrades.

He had with him his water-bottle and a brandy-flask; and with the contents of these, a sandwich or two (from his haversack) made of tinned meat, and a ration of biscuit, he made a meal, as mid-day was now past, and, lighting a cigarette, strove to study the art of being patient.

As he lay there and smoked, numbers of insects, nameless to him— cicadas, huge moths and butterflies—huge in the tropics—buzzed and flitted about him; small birds, the gold and emerald cuckoo, sunbird and finch, with beautiful plumage, flitted from branch to branch overhead; a lizard or chameleon crawled along. Dazed by the heat, and under the influence of the latter, and perhaps of his cigarette, Florian dropped asleep.

From this he was startled by a trumpet sounding the advance, and was roused just in time to see the detachment consisting of the two Lancer Squadrons, the Mounted Infantry, Frontier Horse, and Bengough's Natives resuming their route to the camp, after investigating the ashes of the hut he had quitted, and which had no doubt caught fire from the hot embers of others blown against it by the wind.

But Florian's heart sank within him at the contemplation of what might have been had he slept on—had the trumpet not been sounded, and the troops had ridden away, leaving him helpless in that solitude.

CHAPTER

V.

THE LOADED DICE.

Shafto was located in a quiet hotel in St. Andrew Square, Edinburgh, whither he had come in hope to raise money to meet the difficulties in which he had become involved. When away from the splendid thraldom of Craigengowan—for thraldom he deemed it now—he was daily and nightly in the habit of imbibing more than he would have ventured to do there; thus he was becoming slow of speech, with the fishy eye and the fevered breath of the habitual tippler, even at his years, while in dress he adopted a style that was a curious combination of the dandy and the groom.

The many confiding tailors, jewellers, horse-copers, wine-merchants, and others whom he had honoured by his patronage were now getting beyond all bounds with their importunity and—as he thought—impertinent desire to have their bills settled; while, disgusted with him, Lord Fettercairn had been heard more than once to say, even to old Mr. Kippilaw:

'If Finella had been a boy I should not have cared so much about there being no other grandson of my own to ensure the succession and carry on the title.'

But the peer did not yet know the worst.

Occasional visits to Edinburgh, and still more those to London, were always involving Shafto in one or other disgraceful scrape; for, notwithstanding a most liberal allowance, he was often at his wits' end for money, and was over head and ears in gambling debts. Thus he was a bitter pill to the patriotic peer, his 'grandfather,' and he was on the verge, he feared, of dire disgrace, as a whole lot of post-obits might soon come to light—on the fortune he reckoned would come to him on Lord Fettercairn's death or his marriage with Finella; for with two such prospects the Jew money-lenders and other scoundrels who trade as such, in Pall Mall and elsewhere, under double names, had seen things in a 'rosy' light, and let him thus have 'no end of money.'

And now, as a means of recruiting his exchequer for a time, he bethought him of young Kippilaw, who had been left £30,000 unexpectedly by an

uncle in Glasgow, and his first thought was to flatter and fleece the fellow if he could, though the spruce little W.S. was on the eve of his marriage with one of the many daughters of Lord Macowkay, the eminent senator of the College of Justice; so he invited that gentleman to a quiet little dinner at his hotel, 'Just to pick a bone—sharp eight.'

Little Kippilaw, who was always flattered by the society of a prospective peer, as something to talk about in the Parliament House, accepted with a radiant countenance; and, as he had rather a showy-looking friend who was passing through Edinburgh on his way to Drumshoddy Lodge, he asked permission to bring him.

'Certainly, of course,' said Shafto.

'Major Garallan is a client of the firm.'

'What! the old woman Drumshoddy's nephew?'

'The same.'

'All right; let us have him.'

So the Major came in due course. He was the beau-ideal of a cavalry man—tall, handsome, well set up and put together, dark-complexioned and regular-featured, with his ears and neck scorched by the Indian sun to a hue in which red and bistre were blended; but an awkward accession he proved to Shafto eventually.

The dinner, with its soup, fish, and many entrées, was all that could be desired, from the curaçoa to the coffee, and put Shafto's two guests in excellent humour with themselves and the world generally; the cloth was drawn, the wine and dessert put on, and, seated at the head of the table, Shafto almost forgot his troubles, as he took bumper after bumper of sparkling Pommery-greno, while from the tall windows could be seen the space of the stately square, with its tall central column crowned by the colossal statue, of Melville, and all its many-pillared and palatial banks and public offices whitened by the silver light of the summer moon.

The Zulu War was, of course, spoken of, the mishaps at Isandhlwana and Intombe discussed, though the subject was shirked by Shafto, who cared nothing about it, save in so far as the danger that then menaced Florian; but little Kippilaw, who was a full-blown captain in the Queen's Edinburgh Rifle Brigade, talked a vast amount of 'shop' to the amused Major Garallan, whom he ventured to instruct in the 'new method of attack,' and thereby drew out the latter insensibly to talk a little of his Indian experiences, for he had served in the expedition to Perak, against the Malays, and the Jowaki expedition on the frontier of Peshawur, and been wounded at the storming of Jummoo; affairs that, though small in themselves, went rather beyond a sham fight in the Queen's Park, including the storming of St. Anthony's Chapel and forming a rallying square in the Hunter's Bog.

And now the conversation began to flag, though Shafto had circulated the wine freely, and he thought the time had come to propose 'a little mild play.' One circumstance surprised him—that though they were supposed to be connected by marriage, the somewhat haughty Major never made the slightest reference to the subject.

'A quiet rubber of whist, with a dummy,' suggested Kippilaw.

'With a dummy, no,' said Major Garallan. 'I like poker, but——'

'Poker be hanged!' interrupted Shafto.

At this abrupt speech the Major, a well-bred man, pushed back his chair a little way, while Shafto paused and felt in his waistcoat-pocket a little white square ivory object—of which more anon.

It was arranged that Shafto and Kippilaw should have a mild game of écarté, while Major Garallan smoked, idled, and looked on, a course that the first-named gentleman by no means approved of, as, for cogent reasons, he had an intense dislike of having his play overlooked.

Kippilaw, inflamed by the wine he had taken inconsiderately—while Shafto, cautious to a degree, had not, to use a phrase of his own, 'a hair of his coat turned'—allowed himself to be lured into doubling the stakes again and again; and Shafto, who had his own ultimate end in view, while playing

to all appearance with intense care, allowed himself to lose eventually the sum of £500, for which, as he had not the most remote intention of paying it, he with great liberality gave an 'IOU' to Kippilaw, who, not being an habitual gamester, but by nature and profession cautious and gentlemanly in spirit, was rather scared in accepting the document.

Then a pause ensued in the game, during which more wine—Pommerygreno—was circulated, fresh cards produced, and Shafto invited the Major to play, but he declined somewhat curtly, as Shafto thought.

He then urged Kippilaw to let him have his 'revenge,' and the latter was willing enough to let him have back the IOU if he won it, or any portion thereof, as he disliked to possess such a document signed by the son of a client of the firm, and thought secretly that he would not play a shilling beyond that sum; but he had partaken of too much champagne, which, when the Major's back was turned, Shafto contrived to dash with brandy, and soon the demon of play, rivalry and acquisitiveness overruled the reason of Kippilaw; but the nefarious action of Shafto had not been unnoticed by the Major, who had affected to be twirling his moustache by the aid of a mirror above the high black marble mantelpiece.

Shafto produced a dice-box; he lost, and Kippilaw won, as it was intended he should, and a silly laugh of exultation escaped him.

'Another IOU—you're in luck's way to-night, Kippilaw!' exclaimed Shafto.

'How much have I won?'

'A hundred and fifty.'

The play went on—the dice-box rattled again and again, while the Major, with his back against the mantelpiece, looked silently and curiously, but darkly on. Shafto won back—what he had lost as a lure—his £500, with wonderful celerity, and then another sum of £100, for which Kippilaw gave him a cheque, signed by a very unsteady hand.

'Double or quits,' said Shafto, staking the cheque, with his hand on the dice-box.

'Thanks—but I don't think I'll play any more,' said Kippilaw.

'Oh—indeed—please yourself,' said Shafto scornfully, while biting his lips with anger and disappointment—'but after gaining £500 from me—the devil—are you afraid?'

'No.'

'What then?'

'I have played enough—more deeply than I ever did before.'

'Enough!' repeated Shafto contemptuously.

'Yes.'

'Too much, indeed,' said Major Garallan suddenly; 'and, by Jove, you do right to stop, Kippilaw.'

'What the devil do you mean?' asked Shafto, becoming pale with sheer fury.

'What I say,' replied the officer coolly.

'Who the —— gave you a right to interfere?' demanded Shafto in a bullying tone.

'I have watched your play, sir, for some time past,' replied the Major quietly, 'and know right well how and why the tide of fortune turned so suddenly in your favour.'

An oath escaped Shafto, and snatching up the cards, he hurled the pack to a remote corner of the room.

'What does all this mean?' asked Kippilaw, staring half tipsily and with a scared air at the speakers.

'It means, you goose, that you have been playing with a fellow who is no better than a blackleg,' said the Major, with quiet scorn. 'No, you don't,' he added, grasping, as if with a smith's vice, the wrist of Shafto, who, uttering a cry like a jackal, seized a cut-glass decanter, with the fell intention of hurling it at the speaker's head, but the latter cowed him by one steady glance.

'You shall repent this insolence,' said Shafto, starting to his feet. 'I will teach you to question a man of honour with impunity.'

'Honour!' laughed Garallan.

'You shall hear from me, sir.'

'In what fashion—an action at law?'

'No; one perhaps you may shrink from.'

'Very probably. You don't mean a duel?'

'I do.'

'Where?'

'On the sands at Boulogne.'

'Fool! People don't fight duels nowadays, and if they did, I am not required to fight with a—swindler! That is the word, so let us hear no more high falutin. A man of honour, indeed!'

Garallan burst into a fit of scornful laughter, and Shafto, mad with rage and disappointment, was rushing to grasp the poker, when the former, in a moment, and before the apparently helpless Kippilaw could interfere, if able to do so, in any way, had struck his would-be opponent down, and wrenched from his left hand, which he tore open by main force, something that Shafto had attempted to put in his mouth, and which, on examination, proved to be—a loaded die.

CHAPTER VI.

SHAFTO'S HORIZON BECOMES CLOUDY.

The Major had gone to the 'little dinner' at the desire of Kippilaw, but unwillingly; he had evidently heard something about Shafto—knew him by reputation, and during the meal had treated him perhaps rather cavalierly, which Shafto was too self-assertive or too 'thick-skinned' to perceive, though Kippilaw did.

The little W.S., who had never been in a 'scrimmage' since he left the High School, was desperately scared by the whole affair, and especially by the mauling given to Shafto, the son of a client of the firm, the heir of Lord Fettercairn, by the Major, who made very light of the matter, and called him 'a d——d cad, and worse than a cad.'

When Shafto gathered himself up they were gone, and he heard their footsteps echoing in the now silent square (where the tall column stood up snowy white in the light of the waning moon) as they turned westward along George Street, and a feeling closely akin to that of murder gathered in his heart as he poured the most horrible maledictions on the Major, and drank a deep draught of foaming Pommery-greno, well laced with brandy.

That fellow had spoiled his game, and his nefarious plans against young Kippilaw, whom he regarded as a wealthy pigeon to pluck. No good ever came of a quiet third party watching one's play. He would be even with the Major yet, he muttered, as he ground his teeth; but how? The Major had carried off the loaded dice, and after splitting it open, as doubtless he would, exposure everywhere was sure to follow.

He was wrong in one supposition, however, as the Major quitted Edinburgh next morning for Drumshoddy Lodge, and, of course, would be

very unlikely to expose in public one whom he deemed a connection of his own.

Intending to attribute the whole affair of the loaded dice—alleged to be loaded, he would insist—to a tipsy brawl on the Major's part, to a mistake or confusion, and carry it off somehow, Shafto, driven to desperation by want of money on one hand, even to settle his hotel bill in St. Andrew Square, and by some days of terrible doubt and depression on the other, after writing a private note to Mr. Kenneth Kippilaw about his affairs, and fixing an hour for a visit 'thereanent,' ventured to present himself at that gentleman's chambers, where a shock awaited him.

As he passed through the hall, he saw Madelon—Madelon Galbraith— seated in a waiting-room.

'Madelon here—for what purpose?' thought he, with growing anxiety, as he was ushered into the presence of Mr. Kippilaw, who received him with intense frigidity—even more than frigidity—as he barely accorded him a bow, and neither offered his hand nor rose from his writing-table, but silently pointed to a chair with his pen.

Despite this cold welcome, Shafto's constitutional insolence of thought and bearing came to him with a sense of the necessity for action, for his grim reception by the usually suave and pleasant old lawyer roused all his wrath and spite to fever-heat.

'So—so, sir,' began the latter, 'so you, the heir to the estates and title of Fettercairn, actually tried to rob my simple son by means of a loaded dice till exposed by Major Garallan, to whom my warmest gratitude is due; the split fragments are now in my possession; but I presume it was not on that matter you came to consult me. And, not content with such vile conduct, you sought to taunt, bully, and inveigle the Major into a duel, in which perhaps your superior skill or cunning might achieve his murder. Duels, however, are out of date; but penal servitude is not, so beware, Mr. Shafto— beware, I say—there is a rod in pickle for you, I suspect.'

And as he spoke the keen, glittering eyes of the old lawyer glared at Shafto above the rims of his pince-nez.

'But you come to confer with me about your private debts, Mr. Shafto,' he added, lowering his tone.

'Yes.'

'You know the total amount, I presume?'

'Scarcely.'

'How so?'

'Well, when letters come to me I open the white envelopes and chuck all the d——d blue ones into the fire uninspected.'

'A sensible proceeding—very! How long can it go on?'

'I don't know—perhaps you do,' was the dogged reply.

As if it was useless to ask further questions, Mr. Kippilaw looked over some papers which Shafto had sent for his consideration, and his countenance lowered and his white bushy eyebrows became closely knitted as he did so, while Shafto watched him with an aspect of languid interest which he was far from feeling, and sucked the ivory head of his crutch-stick the while.

'Why, Mr. Shafto,' said Mr. Kippilaw, 'this is rank dishonesty.'

'What is?'

'This mess I am contemplating.'

'Don't talk thus to me; the greatest robbers in the world, after one's own family lawyers——'

'Sir!' interrupted Mr. Kippilaw, smiting the table with his hand, and looking dangerous.

'To business, then,' said Shafto sulkily.

'There's this bill of Reuben Levi, the London money-lender, of which I have a note, drawn originally for £500, at three months, bearing interest at sixty per cent., and renewed three times!'

'Well?'

'The money value to the drawer is not likely to be much at the close of the precious transaction.'

'D—n, I think not.'

'Lord Fettercairn will have to take up these.'

'A few more too, I suspect,' groaned Shafto.

'This is quite as disgraceful as your affair of the cards at that Club in Princes Street.'

'Which?'

'When you were found playing baccarat with ever so many cards too much in the pack. I am sick of you and your affairs, as you call them. The man who can act as you do, in these and other matters, is not likely to discharge the duties that devolve on the proprietor of Craigengowan and the title of Fettercairn, alike teeming with temptations; therefore I think his lordship will put it out of your power to make ducks and drakes of the inheritance, if he takes my advice.'

'Your advice!' thundered Shafto.

'Precisely so,' said Mr. Kippilaw quietly, as he thrust all Shafto's papers into a drawer and locked it. 'Lord Fettercairn has lost all patience with you, sir. People should not incur debts they are unable to pay. I know of no action more mean or contemptible than to make some man—a poor one, perhaps—lose for another's amusements and enjoyments. You ought to consider this.'

'Thank you, Mr. Kippilaw. You are, I believe, a leading elder in your kirk, whatever that may mean; but I'll not have you preach to me.'

'A man should do anything rather than defraud his neighbour.'

'D—n you, you old cur! do you speak of "defrauding" to me—you, a lawyer?' said Shafto, grasping his cane.

'I do,' replied Mr. Kippilaw firmly. Shafto quailed under his gaze, and turned to leave the room. 'Mr. Gyle!' said the lawyer, ere he could do so.

Shafto turned and faced him.

'Ha!—you answer to your name, I see!'

'What do you mean?'

'Simply that I begin to think you are an impostor!'

Shafto glared at him, white with rage and dismay, while a minute's silence ensued.

Perhaps the astute lawyer had read that remarkable essay by Lord Bacon on cunning, wherein he tells us that an unexpected question or assertion may startle a man and lay him open. 'Like to him,' he continues, 'that having changed his name, and was walking in St. Paul's, another came behind him, and called him suddenly by his true one, whereat straightways he looked back.'

'An impostor, dare you say?' exclaimed Shafto, taking one pace to his front.

'Considering your conduct, I begin to think so.'

Shafto felt for a moment or so relieved, and said:

'What the devil do you mean? You had a properly attested certificate of my birth?'

'Attested—yes.'

'Was that not all-sufficient, even for your legal mind?'

'Not—now.'

'Why not now?'

'Because I remember that it is mutilated.'

Shafto winced.

'It is there, however,' said Mr. Kippilaw, pointing with his pen to a green charter box labelled 'Fettercairn,' and Shafto thought that if he did not adopt a high tone he might fail in the matter.

'You scoundrel,' he exclaimed, as he smashed his cane on the writingtable, scattering letters and documents in every direction; 'doubt of my identity is an insult now!'

Mr. Kippilaw did not lose his temper; he puckered up his eyebrows, actually smiled, and looked cunningly at Shafto as he pulled or twitched his nether lip with a finger and thumb. He was evidently reconsidering the situation in his own mind, and coming to the conclusion that there was a mistake somewhere.

Shafto was sharp enough to read this at a glance; he thought of Madelon, and his heart became filled with black fury.

'I think our interview is ended,' said Mr. Kippilaw quietly, as he dipped a pen in the ink-bottle and laid his left hand on a bell. 'You will be good enough to leave my chambers, sir, or I shall have you shown out by the hall-porter.'

There was nothing left for him but to withdraw, and as he did so, Madelon Galbraith, who had been evidently waiting an interview, entered Mr. Kippilaw's room, and as she passed she gave Shafto a terrible glance with her black, sparkling eyes—a glance of hatred and triumph—as she had not forgotten, but remembered with true Highland bitterness, the day of her rough expulsion from Craigengowan, when he had actually hounded a dog upon her.

Shafto shivered; he felt as if an iron network was closing round him, and that a fierce legal light might yet be cast on his secret villainy.

Guilt does not always look to the future. It is as well perhaps, under any circumstances, that we never can see that mystic but certain period.

Smarting under Shafto's unbridled insolence to himself, and acting very probably on some information accorded to him by Madelon Galbraith, whom he desired to remain at his house in Edinburgh, Mr. Kippilaw took means to achieve more—means which he should have adopted immediately after his first interview with Shafto.

Discomfited, there was nothing left for the latter now but to cast himself on the mercy of Lord and Lady Fettercairn in the matter of his debts and involvements; and this, after a few days of doubt, irresolution, and much hard drinking, he resolved to do, and so set out for Craigengowan.

In these few days the strands of Fate had been twisting slowly but surely into a fatal coil!

CHAPTER VII.

THE SQUARE AT ULUNDI.

In the camp at the Entonjaneni Mountain the troops had two entire days' rest, which enabled Florian to recover completely from the effects of the accident which had befallen him in the pursuit of the Zulus.

In the afternoon of the 28th a telegram came announcing to Lord Chelmsford that Sir Garnet Wolseley had arrived, that he had assumed the entire command, and requesting a plan of the campaign, which, apparently, Lord Chelmsford, having conducted thus far, was resolved to finish for himself, as he did.

With the same messengers came the mails for the troops, and, to Florian's delight, there came a letter from Dulcie—we say delight at first, for that sentiment soon gave place to one of anxiety.

At the sight of her handwriting, his heart went back in a day-dream to the banks of the Yealm and the Erme and to the exquisite Devonshire lanes where they had been wont to wander hand in hand together—lanes bordered by banks of pale green ferns, while the golden apples hung in clusters overhead.

Isolated now amid the different worlds in which each lived, these two were tenderly true to each other, at those years when they who have been boy and girl lovers usually forget, or form new attachments.

Florian was struck by a certain confusion in the letter of Dulcie, which seemed to have been written in haste and under the pressure of some excitement, so that at times it was almost incoherent.

'I am not superstitious, as you know, dearest Florian, but I dislike the brilliant month of June more than any month in the year,' she wrote. 'Papa died in June, leaving me alone in the world and so poor—hence I have always strange forebodings of unseen evils to come—evils that I may be powerless to avert; thus June is ever associated in my mind with sorrow, death, and mystery. It is then I have restless nights and broken dreams of trouble haunting me—even of hideous forms seen dimly, and I leave my pillow in the morning more weary than when I laid my head upon it at night. It is June again, and I am in trouble now.'

She proceeded then to describe her persecution by Shafto, who was again returning after an absence; that his presence, conjoined to the taunts, suspicions, and tone of Lady Fettercairn, made life at Craigengowan a burden to her, and that she had determined on flight from the house—from Scotland indeed—but where she was to go, or what she was to do, she knew not. She had resolved not even to consult her only friend Finella, so that, by the time her letter reached him, she would be out once again on the bosom of the cold world!

So ended this distressing and partly incoherent letter, which was the last Florian received from Dulcie Carlyon, and by the tenor of it there seemed a futility in sending any reply to Craigengowan, as too probably she must have left it some weeks ago.

'If killed to-day or to-morrow—anyway, before Cetewayo is caught—I'll never know, probably, how my darling gets over her trouble,' thought Florian simply but sadly.

There came by the same post no letter for the absent Hammersley, so Florian concluded that Finella Melfort must have seen through the medium of the public prints that he had sailed for Europe on sick leave.

It was vain for him to imagine where and amid what surroundings Dulcie was now, and doubtless with very limited means; it was a source of absolute agony to him at such a time, when he was so helpless, so totally unable to assist or advise her, and he seemed as in a dream to see the camp, with its streets of white tents and soldiers in thousands loitering about, or stretched on the grass, laughing, chatting, and smoking in the sunshine.

In the immediate foreground, on the branch of a tree, hung the skinned carcase of an eland, from which a powerfully built Hottentot of the Natal Contingent, all nude save a pair of breeches, was cutting large slices with a huge knife, and dropping them into Madras cowrie baskets prior to cooking them in small coppers half full of mealies.

A rich plain stretched away to the north; beyond it were mountains covered with grass and dotted by clumps of trees, and in some that grew close by the camp, numbers of beautiful squirrels were hopping from branch to branch in the sunshine.

Ulundi was now only sixteen miles distant from our outposts, and from thence came the last messengers of Cetewayo, bringing with them as a peace-offering the sword of the Prince Imperial—the sword worn by his father, too probably at Sedan, with a secret message—written by Cornelius Vign, the Dutch trader—to Lord Chelmsford, telling him that if he advanced on Ulundi to do it with strength, as the forces of Cetewayo were many, many thousands strong.

On the 1st July the division marched again.

Florian had been scouting with his squadron all the preceding day and far into the night, and lay in his tent weary and fagged on a ground sheet only, without taking off either accoutrements or regimentals. There, though worn, he had dreams, not of Dulcie, but of his dead comrade, jovial Bob Edgehill, and the little song the latter was wont to sing came to his dreaming ears:

'Merrily lads, so ho! Some talk of a life at sea; But a life on the land, With sword in hand, Is the life, my lads, for me.'

Then he started up as he heard trumpet and drum announcing the 'turn out'—the latter with the long and continued roll there is no mistaking. A hasty breakfast was taken—scalding coffee drunk standing beside the camp fires—the tents were struck, the waggon teams were inspanned, the Mounted Infantry went cantering to the front, and the march was begun.

Beautiful though the district looked when viewed from Entonjaneni, the country to be traversed proved a rugged one, covered with tall reed-like grass of giant height, that swayed slowly in the wind, interspersed with mimosa scrub and enormous cacti, with leaves like sabre-blades; but by half-past one a.m. the White Umvolosi was reached.

More scouting in a dark and moonless night fell to the lot of Buller's Horse and Florian's Mounted Infantry. They could hear the war-song of the vast Zulu army—unseen in the darkness, but chiefly posted at fords on the river, loading the still, dewy air, rising and falling with wild, weird, and impressive effect, now apparently near, now distant; but so mighty ever and anon was the volume of sound that it seemed to corroborate the alarming message of Cornelius Vign. Among other sounds were the awful shrieks of a dying prisoner, whom they had impaled on the bank of the stream.

Much scouting, scampering about, and skirmishing by 'bank, bush, and scaur' followed for three days, and the 4th of July saw the division on its way to fight the great and final battle of the war, before Wolseley could come on the ground—Ulundi.

The sun was well up in the sky, when the column crossed the river at a point where sweet-scented bushes, graceful acacias, gigantic convolvuli, and wild guava fringed its banks, where the bees were humming, and the Kaffir vultures hovering over the slain of a recent skirmish; and splendid was its aspect in the brilliant morning light—the 17th Lancers with their striking uniform and 'pennoned spears, a stately grove'—the infantry, not clad in hideous 'mud-suits,' but in their glorious scarlet, their polished bayonets and barrels shining in the sun, while in the hollows under the shadows of the great mountains, shadows into which the light of day had scarcely penetrated as yet, the impis or columns of the Zulus were gathering in their sombre and savage thousands.

'The troops will form in hollow square!' was now the General's order, and, with other aides-de camp, Villiers, cigar in mouth, and with flushed cheek and brightening eye, went cantering along the marching column, with the details of that formation for the advance—the first instance of such a movement in modern war, since William Wallace of Elderslie, the uncrowned King of Scotland, instituted such a system at the battle of Falkirk, and consequently he, as Green tells us in his 'History of the English People,' was actually the first founder of 'that unconquerable British Infantry,' before which the chivalry of Europe went down.

As formed by Lord Chelmsford on that eventful 4th of July, the infantry on the four sides of his oblong square marched in sections of fours, with all cavalry and other mounted men scouring the front and flanks, Shepstone's Basutos covering the rear, with the cannon in the acute angles of three faces of the square; all waggons and carts, with stores and ammunition, in the centre.

This was about eight in the morning, and with colours flying and bands playing merrily in the sunshine, this huge human rectangle marched in a north-easterly direction, past two great empty kraals and a vast green

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